Many xenobiotic chemicals in the environment mimic the estrogens in human body resulting in drastic changes in estrogenic functions. The prenatal and neonatal periods of life are vulnerable to environmental estrogen exposure. The alterations that occur during these critical stages of development are the result of long-term changes in the neuroendocrine system and the process is called 'imprinting'. As a consequence of imprinting, the altered cytochrome P450 enzyme functions eventually lead to disruption of normal metabolic processes in adult animals. Eventually, adult animals are predisposed to biochemical insult in specific target organs when they are faced with exogenous chemical challenge. The objective of this proposed research is to elucidate the mechanism of altered imprinting for xenobiotic metabolism and genotoxicity. In this proposal the principal investigator will test the hypothesis that neonatal exposure to resveratrol, a phytoestrogen alters subsequent metabolism and genotoxicity of benzo( a)pyrene (BaP: a toxic and carcinogenic polycyclic aromatic hydrocarbon compound) when the animals reach adulthood. To test this hypothesis the following specific aims are proposed i) to study the in vivo metabolism of BaP in adult F-344 male rats exposed neonatally to resveratrol, and ii) to investigate the relationship between altered imprinting and formation and persistence of BaP-DNA adduets after oral exposure to BaP in target tissues of rats that received resveratrol neonatally. The PI's expectation is that findings from this research will provide valuable information on the underlying mechanisms of altered imprinting for activation/detoxification metabolism of carcinogenic chemicals and genotoxicity. This approach is significant in that it contributes to a greater understanding of the role played by neonatal resveratrol exposure on modulation of BaP metabolism in adulthood and the mechanism by which resveratrol potentiate or attenuate BaP induced promutagenesis.